Abstract: This study investigated gene expression of drug resistance factors in biopsy tissue samples from hepatocellular carcinoma (HCC) patients undergoing chemotherapy by platinum complex. Liver biopsy was performed to collect tissue from the tumor site (T) and the non-tumor site (NT) prior to the start of treatment. For drug-resistant factors, drug excretion transporters cMOAT and MDR-1, intracellular metal binding protein MT2, DNA repair enzyme ERCC-l and inter-nucleic cell transport protein MVP, were investigated. The comparison of the expression between T and NT indicated a significant decrease of MT2 and MDR-1 in T while a significant increase in ERCC-1 was noted in T. Further, expression was compared between the response cases and non-response cases using the ratios of expression in T to those in NT. The response rate was significantly low in the high expression group when the cutoff value of cMOAT and MT2 was set at 1.5 and 1.0, respectively. Furthermore, when the patients were classified into A group (cMOAT ≧ 1.5 or MT2 ≧ 1.0) and B group (cMOAT < 1.5 and MT2 < 1.0), the response rate of A group was significantly lower than B group when we combined the cutoff values of cMOAT and MT2. It is considered possible to estimate the therapeutic effect of platinum complex at a high probability by combining the expression condition of these two genes.
Keywords: canalicular multispecific organ anion transporter; chemotherapy; drug-resistance; hepatocellular carcinoma; metallothionein; platinum complex
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Sakurada, T.; Yoshikawa, M.; Sunaga, M.; Kobayashi, E.; Satoh, N.; Yokosuka, O.; Ueda, S. Expression of Drug-Resistant Factor Genes in Hepatocellular Carcinoma Patients Undergoing Chemotherapy with Platinum Complex by Arterial Infusion. Pharmaceutics 2010, 2, 300-312.
Sakurada T, Yoshikawa M, Sunaga M, Kobayashi E, Satoh N, Yokosuka O, Ueda S. Expression of Drug-Resistant Factor Genes in Hepatocellular Carcinoma Patients Undergoing Chemotherapy with Platinum Complex by Arterial Infusion. Pharmaceutics. 2010; 2(3):300-312.
Sakurada, Tomoya; Yoshikawa, Masaharu; Sunaga, Masahiko; Kobayashi, Eriko; Satoh, Nobunori; Yokosuka, Osamu; Ueda, Shiro. 2010. "Expression of Drug-Resistant Factor Genes in Hepatocellular Carcinoma Patients Undergoing Chemotherapy with Platinum Complex by Arterial Infusion." Pharmaceutics 2, no. 3: 300-312.